Exubera. Inhale therapeutic systems

Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first quarter of 2003. In August 2001, Lehman Brothers predicted that launch would take place in the first half of 2002 and that the product would make sales of $475 million in 2003, rising to $875 million in 2004. In the same month, Deutsche Bank predicted that there would be worldwide sales of $50 million in 2003, rising to $400 million in 2005. At this time, analysts at Credit Suisse predicted a launch of the product in 2003, with sales of $70 million in that year, rising to $550 million in 2005. By October 2001, Deutsche Bank predicted sales of $50 million in 2004 and $250 million in 2005. In September 2001, Morgan Stanley predicted sales of $500 million in 2002, rising to $1250 million in 2006.     

Tegaserod (Novartis)

Novartis has developed and launched tegaserod, an aminoguanidine indole 5-HT(4) receptor partial agonist, for the potential treatment of constipation-predominant irritable bowel syndrome (IBS) [286804], [311514] and other functional GI disorders, such as gastroesophageal reflux disease (GERD), chronic constipation and functional dyspepsia [342937], [362853]. It was launched in Mexico for IBS in July 2001 [416879] and in the Czech Republic, Venezuela and Colombia by October 2001. By this time, the product had also been approved in Switzerland [427419]. In September 2001, launch of the product for GERD, chronic constipation and functional dyspepsia was expected after 2003 [422828]; later in October 2001, the launch dates for the latter two indications were anticipated for 2004 [427419], [431614]. In December 2000, Merrill Lynch predicted sales of SFr 150 million in 2001, rising to SFr 612 million in 2004, larger than the September 2000 predictions of SFr 120 million in 2001 rising to SFr 378 million in 2004 [394812], [383742]. Later in February 2001, Merrill Lynch predicted sales of SFr 150 million in 2001 rising to SFr 785 million per annum in 2005, assuming a US launch during the third quarter of 2001 [411704]. Following the withdrawal of the MAA and then the rejection of tegaserod's NDA by the FDA, in June 2001, Merrill Lynch progressively revised its 2005 sales forecasts from SFr 1.1 billion to SFr 950 million and then to SFr 375 million [422783]. In June 2001, Merrill Lynch also suggested that there was a significant possibility that tegaserod would never reach the market. In August 2001, Deutsche Bank estimated sales of SFr 200 million in 2004 and SFr 550 million in 2005 [422674]. Analysts at Credit Suisse predicted in October 2001, that there was only a three in ten chance that tegaserod would ever reach a major market following the issuance of a 'non-approvable' letter by the FDA in June 2001. They predicted sales of SFr 5 million in 2001, rising to SFr 325 million in 2005 [426409].     

Duloxetine Eli Lilly

Duloxetine is a serotonin (5-HT) and norepinephrine (NE) uptake inhibitor in pre-registration for depression. In vivo studies demonstrate that duloxetine inhibits 5-HT and NE transporters and this may induce an antidepressant effect [159168]. In humans, duloxetine has a low affinity for most 5-HT subtypes and for muscarinic, histamine H1, alpha1-adrenergic, alpha2-adrenergic and dopamine D2 receptors [444103]. Thus, it is not surprising that the meta-analysis of four recent clinical studies suggests duloxetine is a potent and well-tolerated antidepressant [429723]. By December 2001, Lilly had filed an NDA for depression. The launch of duloxetine is planned for the second half of 2002 [434250], [436220]. In April 2002, filing for stress urinary incontinence was anticipated for later in 2002 [456894]. Analysts at Banc of America predicted in April 2002, that the drug will be launched in the first quarter of 2003. The company projects US $400 million in revenue in 2003 and anticipates duloxetine to reach peak sales of over US $1 billion [450920]. Analysts at Morgan Stanley, projected US $25 million in sales in the fourth quarter 2002, rising to US $900 million in 2006 [450937]. At the same time, Credit Suisse First Boston anticipated launch for late 2002, with US $220 million in duloxetine revenues in 2003 and US $457 million in 2004 [450936].     

Conivaptan (Yamanouchi)

Yamanouchi is developing conivaptan, an orally active vasopressin V1A and V2 antagonist for the potential treatment of heart failure, edema and hyponatremia. The company anticipated launch of the product for hyponatremia in 2002 [362201]. By May 2001, Yamanouchi was continuing phase II trials in Japan for hyponatremia and heart failure, and in the US and Europe for heart failure, and phase III trials in the US and Europe for hyponatremia [411763]. In July 2000, it had been reported that conivaptan was undergoing phase III trials in both the US and Europefor hyponatremia and heart failure [377561]. In April 1998, Warner-Lambert (now Pfizer) acquired the rights to YM-087 for US, South America, Europe and Africa, while Yamanouchi retains copromotion rights, but by November 2000, Pfizer had cancelled its licensing contract to market the drug in the US [397901]. In September 2001, analysts at Morgan Stanley predicted launch of conivaptan for hyponatremia in the US between 2004 and 2005 [422782]. In October 2001, analysts at Credit Suisse First Boston predicted that an NDA would be filed in 2002 followed by launch in 2003, with peak annual sales of $50 million and $300 million for hyponatremia and heart failure, respectively [427028].     

ZD-1839 (AstraZeneca)

AstraZeneca is developing ZD-1839, an inhibitor of epidermal growth factor receptor 1 (EGFR1) tyrosine kinase, for potential treatment of cancers which overexpress EGF receptors, including non-small cell lung cancer (NSCLC) and pancreatic cancer [196279], [270898]. Phase III studies had started by August 2000 [349551], [350295], [353050], [377656], with first results being expected at the 2001 meetings of the American Association for Cancer Research (AACR) and the American Society for Clinical Oncology (ASCO). The US FDA has issued ZD-1839 with Fast Track status [350295], [353050]. In September 2000, the company expected global NDA filing to take place at the end of 2001, with launch in the next four to five years [383469]. In January 1999, ABN Amro predicted sales of US $25 million in 2004 rising to $82 million in 2005 [316250]. In March 1999, Lehman Brothers predicted a 30% probability that the drug would reach worldwide markets and be launched onto the market in 2004 [336599]. In June 2000, Deutsche Bank predicted sales of US $8 million in 2002, rising to $100 million in 2003 [374500]. In September 2000, analysts Merrill Lynch predicted a launch in 2002 with sales estimated at UK 50 million pounds, rising to 360 million pounds in 2004, while in December 2000, the analysts predicted a filing date in the fourth quarter of 2001 [383742], [396280]. Also in December 2000, Lehman Brothers predicted a filing date late in 2001, and a possible Fast Track review. They also estimated peak sales of US $1 billion [394606].     

Linezolid Pharmacia Corp

Linezolid is an oxazolidinone developed by Pharmacia (formerly Pharmacia & Upjohn) for the treatment of multi-resistant Gram-positive infections [187765,317456]. It binds to ribosomal 50S subunits, most likely within domain V within the 23S rRNA peptidyl transferase and a secondary interaction with the 30S subunit. This results in inhibition of the initiation of protein translation at an early point, which is probably N-formylmethionyl-tRNA [335843]. No direct action on DNA or RNA synthesis has been observed [220169]. Linezolid resistance due to a 23S rRNA mutation may emerge in Enterococci during therapy with this antimicrobial, and may be associated with clinical failure [368652]. Following FDA approval, linezolid was launched in May 2000 [368526,368652]. In April 2000, the FDA approved linezolid injection, tablets and oral suspension for the treatment of patients with infections caused by Gram-positive bacteria. It is indicated for adults in the treatment of nosocomial pneumonia, community-acquired pneumonia (CAP), complicated and uncomplicated skin and skin structure infections and vancomycin-resistant enterococcus (VRE) infections caused by methicillin-resistant Staphylococcus aureus (MRSA), VRE faecium and penicillin-susceptible Streptococcus pneumoniae [363503]. The FDA, however, did not grant Pharmacia indications for linezolid in the treatment of CAP due to either penicillin-resistant S aureus (PRSA) or MRSA. In May 2000, Merrill Lynch predicted sales for 2000 to be US $50 million, rising to US $760 million in 2004 [366910]. In February 2000, P&U predicted that peak sales of the drug had the potential to reach in excess of US $750 million [358429]. In February 1999, Morgan Stanley Dean Witter predicted sales of US $40 million in 2000 rising to US $275 million in 2005 [319855]. In December 1998, Deutsche Bank predicted sales of US $100 million in 2000 rising to US $300 million in 2002 [316769].     

AZD-2563 AstraZeneca

AstraZeneca is developing AZD-2563, an oxazolidinone with a novel mechanism of action, for the potential treatment of gram-positive bacterial infections, including those caused by multidrug-resistant strains [349551], [399542]. As of December 2001, AZD-2563 had completed an escalating-dose phase I trial in the UK and was being developed in the US [433897]; at this time, AstraZeneca did not expect launch until after 2004 [431673]. In October 2001, Morgan Stanley estimated launch in 2004 with sales of US $20 million in that year, rising to US $46 million in following years [429700].     

Deramciclane (Egis)

Egis, in collaboration with Orion Pharma and Pharmacia, is developing deramciclane, a 5-HT(2A) antagonist and a 5-HT(2C) inverse agonist, as a potential treatment for anxiety disorders [300642]. The compound was also in development for epilepsy but no recent development has been reported for this indication. As of May 2001, comprehensive phase III studies with deramciclane in ten European countries were progressing according to plan [399853], [408534]. By August 2001, phase III studies were also underway in South Africa [420313]. In November 2001, Pharmacia indicated that NDA filing is expected to take place in 2004 [431903]. In February 2001, Orion announced its intention to commercialize deramciclane globally [399853]. In August 2001, Orion and Pharmacia signed an agreement under which the two companies were to collaborate in the development and commercialization of deramciclane in the US [420313]. Analysts at Morgan Stanley predicted in November 2001, that deramciclane would make sales of $25 million in 2004, rising to $150 million in 2005 [435320]. Analysts at Lehman Brothers predicted in December 2001, that deramciclane had a 75% chance of being marketed by 2004, with peak sales potential of $450 million [434768].     

MethyPatch Noven

Noven Pharmaceuticals is developing a transdermal patch formulation of methylphenidate for the treatment of attention deficit hyperactivity disorder (ADHD) [325808]. Phase III trials were completed in February 2002 [438893]; at this time, the company predicted a 2003 launch for the product [441478]. In April 2002, based on pivotal phase III trial results, Noven expected to file an NDA with the FDA in mid-2002 and to launch the product in the second half of 2003 [445181]. In June 2002, the NDA was filed [456552]. The original phase III trials were completed in the first quarter of 2001 [407254]. However, preliminary analysis of the phase III trial, reported in April 2001, suggested that a supplemental study would be required to support the filing [403771]. At this time, an NDA filing, originally planned for the second quarter of 2001, was rescheduled for the first half of 2002 [400122], [407640], [410285], [441478]. As of August 2001, the supplemental study was expected to begin in autumn of that year [417877]. In October 2001, enrolment was initiated in Noven's pivotal, double-blind, placebo-controlled, multicenter phase III study of MethyPatch [427321], and it was completed in February 2002 [438893]. In May 2001, the company was issued patent US-06210705 relating to the transdermal delivery of methylphenidate for the treatment of ADHD [410285]. In June 2001, ABN AMRO predicted sales of US $61 million in 2002, rising to US $74 million in 2005 [422762]. Analysts at Morgan Stanley predicted in May 2002 that the product would make US sales of US $9.1 million in 2003, rising to US $22.5 million in 2006 [454573].     

Oprelvekin. Genetics Institute

Genetics Institute has developed and launched oprelvekin (rhIL-11; Neumega), a recombinant form of human IL-11. In November 1997, the FDA cleared oprelvekin for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in susceptible patients with non-myeloid malignancies 12703021. The product was launched at the end of 1997 [312556]. By December 1999, phase III trials for Crohn's disease (CD) were underway [363007]. Genetics Institute had commenced a 150-patient phase II trial for mild-to-moderate CD and mucositis and the company planned to file regulatory procedures for the indication of CD in 1999 [271210]. An oral formulation for this indication has been developed. Oprelvekin is also undergoing phase I clinical trials for colitis [396157], phase II clinical trials for rheumatoid arthritis [413835] and clinical trials for psoriasis [299644]. In March 1997, Wyeth-Ayerst became the licensee for Europe, Africa, Latin America and Asia (with the exception of Japan). Genetics Institute holds marketing rights for North America [239273]. In Japan, oprelvekin is being developed by Genetics Institute and Yamanouchi; phase III trials have commenced [295049] and were ongoing in May 2001 [411763]. In April 1996, analysts at Yamaichi estimated launch in 2001 and maximum annual sales of over yen 10 billion [215896]. In January 1998, Morgan Stanley Dean Witter predicted Yamanouchi's share of sales to be yen 1 billion in 2001, rising to yen 2 billion in 2002 [315458]. Sales of oprelvekin were US $34 million for Genetics institute in fiscal 2000 while, in July 2001, Credit Suisse First Boston estimated that this figure will be US $30 million and US $34 million in 2001 and 2002, respectively [416883].     

Etanercept. Immunex

Immunex has developed and launched etanercept, a soluble TNF receptor (TNFR) fusion protein, for the treatment of rheumatoid arthritis (RA). It has also been developed for various TNF-mediated conditions such as congestive heart failure, endometriosis and multiple sclerosis. Etanercept has been launched as a second-line agent in the US for the treatment of moderate-to-severe RA and can be used in conjunction with methotrexate in patients unresponsive to methotrexate alone. It is also available in the EU. In 2000, it was in phase III trials for psoriatic arthritis and an NDA filing for this indication was expected for the first half of 2001. In July 2001, the sBLA was filed, and in September 2001, the FDA granted the sBLA Priority Review status. As of January 2001, etanercept was in phase III trials for congestive heart failure, with sNDA filing expected in 2002; however, by March 2001, these had been halted, as it did not appear that statistical significance would be reached for the efficacy endpoints. Further data analysis was being undertaken at this time, before a final decision was taken. In April 2001, Merrill Lynch reported that development for this indication was to be halted. Sales for the drugs first full quarter on the market in 1999 were US $59.7 million. By November 1999 the drug had made sales of US $500 million; Immunex expected the drug to generate over US $2 billion in annual sales by 2004. In September 2000, Merrill Lynch reported that if sales of the drug continued at the present rate then it is likely that demand would temporarily outstrip supply in 2001. Resolution of the supply issue was expected by 2002. Also in September 2000, Merrill Lynch lowered their estimate of sales in 2001 from US $1 billion to $927 million. In the long-term, Merrill Lynch believed that the drug has the potential to exceed US $5 billion in sales in the US. In April 2001, Merrill Lynch predicted that etanercept prescribed for RA would generate sales of US $71 in 2002 rising to US $600 million in 2005. In October 2001, Morgani Stanley reported that Enbrel continues to be the primary source of revenue of Immunex (US $198.1 million). It was also reported that if launched for CHF, an estimated peak year revenue was likely to be US $500 million. The company maintains a website containing additional information about etanercept at http://www.enbrelinfo.com.     

(S)-Zopiclone Sepracor

(S)-Zopiclone, a cyclopyrrolone sharing activity with benzodiazepines in the CNS, is a short-acting sedative being developed by Sepracorfor the potential treatment of sleeping disorders. In August 2000, the company had completed phase II trials of (S)-zopiclone for insomnia [380377]; by September 2000, patient enrollmentfor phase III studies for insomnia was completed and the trial initiation was planned for October 2000 [381361]. Merrill Lynch expects US filing to take place in the second half of 2001 [383230]. Sepracor was granted US-05786357 in August 1998 covering methods and compositions of (S)-zopiclone in the treatment of sleeping disorders [342938]. In August 2000, Merrill Lynch predicted (S)-zopiclone sales of US $30 million in 2002, rising to US $150 million in 2004 [383230].     

Duloxetine Eli Lilly & Co

Lilly is developing duloxetine, a 5-HT and norepinephrine uptake inhibitor as a potential treatment for depression and urinary incontinence. In Japan, it is being jointly developed with Shionogi [187401]. Phase III trials for depression and phase II trials for urinary incontinence are underway in Japan [296442,328887]. Lilly expects to file for depression in 2002 and phase III trials for urinary incontinence are planned to start enrollment by the end of 2000 [358429,370526,373870]. Duloxetine has a half-life of 10 to 15 h in humans, and parameters reach a steady-state after 3 days of daily administration. In a 6-week, open-label study duloxetine was safe and well tolerated in 79 clinically depressed patients. Clinical response occurred in 78% of patients, and remission occurred in 60%. Insomnia and nausea occurred with an incidence of 20% [300881]. Duloxetine may offer advantages over existing antidepressants, such as Lilly's fluoxetine, because of faster recovery and fewer side effects [190226]. In June 2000, Morgan Stanley Dean Witter predicted duloxetine would reach the market in 2002 with annual sales in this year of US $50 million, rising to $200 million in 2005 [373870]. In February 1999, Deutsche Bank predicted Lilly's sales at US $200 million in 2002 rising to $400 million in 2003 [316821]. In May 2000, Deutsche Bank had made further predictions, stating that filing for duloxetine is expected in the fourth quarter of 2001, and peak sales are expected to exceed US $500 million. Also in February 1999, Lehman Brothers predicted the first major launch date (US and ex-US) to be 2002, with the year of peak sales to be 2008 [319225]. In August 1999, this prediction changed, and the expected launch date became 2001, with an 80% probability of reaching the market and sales peaking at US $150 million in 2012 [349228].     

Ximelagatran (AstraZeneca)

AstraZeneca (formerly Astra) is developing ximelagatran, an orally active thrombin inhibitor and prodrug of melagatran, for the potential prevention and treatment of venous thromboembolism (VTE) in hip and knee replacement, for prevention of stroke in atrialfibrillation (AF) and for post acute coronary syndrome. As of December 1999, the compound was undergoing phase III trials for the prevention of VTE [349551]; these were ongoing in December 2001. By December 2000, ximelagatran had entered phase III trials for the prevention of stroke in atrial fibrillation [395212]. In September 2000, the company expected global NDA filing for this indication to take place in the middle of 2001 [383469]; however, in December 2000 this was revised to the second half of 2002 [395212], and in March 2001, to the second quarter of 2003 [402040], [416882], [431673]. By December 2000, a phase II trial was underway of ximelagatran as a potential treatment following myocardial infarction [395237]. In December 2001, early phase clinical trials were ongoing for post acute coronary syndrome [431673]. By December 2001, EU and US filings for VTE prevention were anticipated in the third quarter of 2002 and the second quarter of 2003, respectively [3144721, [350050], [431673]. Exanta is the trade name for both melagatran and ximelagatran. In 1998, marketing of ximelagatran in the US was to be assigned to the Astra/Merek joint marketing venture, prior to the merger [276577]. In April 1999, ABN predicted sales of 4 pounds million in 2003 [328676], [394606]. In December 2000, Lehman Brothers estimated peak sales to be $1.4 billion [394606]. At the same time, ABN-AMRO predicted peak sales of more than $1 billion [395237]. In June 2000, Deutsche Bank predicted sales of $70 million in 2002, rising to $245 million in 2003 [374500]. In September 2000, Merrill Lynch predicted sales of 125 pounds million in 2002, rising to 625 pounds million in 2004 [383742]. In February 2001, Merrill Lynch estimated that peak sales would reach $924 million in 2005 [429697].     

Omapatrilat. Bristol-Myers Squibb

Bristol-Myers Squibb (BMS) is developing the vasopeptidase inihibitor, omapatrilat, a dual inhibitor of angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP), for the potential treatment of cardiovascular diseases such as hypertension and heart failure [306287]. An NDA for the use of omapatrilat in hypertension was filed with the FDA and the regulatory authorities in the EU in December 1999 [351207], [353287]. In April 2000, BMS voluntarily withdrew the NDA in response to questions raised by the FDA regarding the comparative incidence and severity of an infrequent side effect (angioedema) reported within the NDA database. Prospective controlled clinical studies in patients with hypertension and heart failure were to continue. In May 2001, BMS reported that its blinded omapatrilat hypertension study was continuing and, pending supportive results from a data analysis anticipated in late summer/early autumn 2001, the company expected to refile an NDA with the FDA [409203]. In July 2000, BMS reported that it planned to conduct a multinational, 25,000 patient study (OCTAVE - Omapatrilat Cardiovascular Treatment Assessment Versus Enalapril) to compare the efficacy and safety of omapatrilat against enalapril in the treatment of hypertension [374909]. The OCTAVE trial was expected to generate data by mid-2001, which could allow for a launch by early 2002 [380280]. Phase III trials for hypertension had commenced by January 1998 [273646]. In January 2001, Merrill Lynch expected BMS to refile its NDA with the FDA in the second half of 2001 [395423]. In February 2001, Credit Suisse First Boston made a similar prediction, adding that it believed BMS would launch the drug in late 2002 or early 2003. The analysts also predicted peak sales for the drug of $585 million in 2005 [399484]. In May 2001, Merrill Lynch estimated sales of $1.8 billion in 2005 [411811].     

Fulvestrant (AstraZeneca)

Fulvestrant (Faslodex) is an estrogen receptor (ER) downregulator under development by AstraZeneca for the potential treatment of breast cancer [172191], [237518], [314472], [349551]. In March 2001, an NDA was filed in the US for the second-line treatment of advanced breast cancer in postmenopausal women who have progressed on prior hormonal therapy [403574], [434825]; in December 2001, AstraZeneca was expecting to launch the compound in the US in thefirst half of 2002 [431887]. In August 2001, late-stage clinical trials were ongoing in Japan for breast cancer [422343]. Fulvestrant also has potential in the treatment of other estrogen-responsive tumors, such as uterine tumors [178081]. By 1997, fulvestrant was in phase II trials for uterine fibroids [272162], and by February 1999, it was reported that phase II trials for endometriosis were ongoing [314472], [336599]. However, no development has been reported for these indications since that time. In October 2001, Morgan Stanley expected launch in 2002, with estimated sales of $80 million in 2002 rising to $208 million in 2007 [429700]. Analysts at Lehman Brothers predicted in December 2001, that the product has a 90% chance of making it to market in 2002, with peak sales potential in this year of $800 million [434768].     

MK-0991 (Merck & Co)

Merck is developing the echinocandin-type antifungal, MK-0991 (L-743872), a beta-1,3-glucan synthesis inhibitor. It is currently undergoing phase III trials for the potential treatment of systemic fungal infections. The compound entered phase II clinical trials in late 1996. It was administered iv once daily and showed antifungal activity in vitro and in vivo against Candida (including azole-resistant Candida), Aspergillus and certain other fungi. The in vitro activity of MK-0991 has been confirmed by several studies. In November 1998, Morgan Stanley Dean Witter predicted worldwide sales of 40 million USD in 2000, rising to 275 million USD in 2005. In February 1999, Credit Suisse Dean Witter predicted sales of 65 million USD in 2001, rising to 330 million USD in 2002. In February 1999, Lehman Brothers predicted 60% probabilities of US and ex-US market penetrations and launch onto these markets by 2000. Expected sales are predicted to be 15 million USD (in the US) and 10 million USD (ex-US) in 2000, rising to 200 USD million and 175 million USD respectively in 2002. Peak annual sales of 500 million USD (US) and 500 million USD (ex-US) are predicted in 2008.     

Synercid Aventis

Rh?ne-Poulenc Rorer (RPR) developed Synercid (RP-59500), an injectable synergistic combination of quinupristin and dalfopristin as a treatment for a variety of infections caused by Gram-positive anaerobic bacteria. The treatment was approved in the UK in July 1999, for use in patients with nosocomial pneumonia, skin and soft tissue infections and clinically significant infections due to Enterococcus faecium when there is no other active antibacterial agent [337556,335257]. It was launched in the UK and the US in September 1999 [342899]. In December 1999, Synercid successfully completed the Mutual Recognition Procedure in the EU under Aventis Pharma for use in patients with these infections [351525]. In September 2000, Merrill Lynch predicted first-year sales in 1999 of Euro 15 million, rising to Euro 171 million in 2004 [384874]. In January 1999, BT Alex Brown predicted sales of US $88 million in 1999 rising to US $450 million in 2002 [318220]. In April 1999, ABN Amro predicted annual sales of DM 30 million in 1999, rising to DM 150 million in 2002 [328676].     

Telithromycin. Aventis Pharma

The ketolide telithromycin (HMR-3647; Ketek), a derivative of clarithromycin, has been launched by Aventis Pharma (formerly Hoechst Marion Roussel) for the treatment of respiratory tract infections with gram-positive or gram-negative cocci, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, intracellular pathogens, atypical microorganisms, toxoplasma or anaerobic bacteria. By May 2001, filings in the US and EU had been completed and a filing in Japan was expected to take place in the fourth quarter of 2001. In July 2001, telithromycin was granted marketing authorization by the EC for the treatment of community-acquired respiratory tract infections, including those caused by bacteria resistant to commonly used antibiotics. In October 2001, the product was launched in Germany. In March 2000, telithromycin was submitted to the US FDA and the EMEA, under the EU centralized approval procedure, for approval for the treatment of community-acquired pneumonia (CAP), acute sinusitis, acute exacerbations of chronic bronchitis and tonsillitis/pharyngitis. The company had expected to launch the product in early 2001. The CPMP issued a positive opinion for all four indications on April 23 2001. In September 2001, the company indicated that it expected the product to be launched in Japan in 2002. The FDA's Anti-infectives Advisory Committee was due to review telithromycin for all the submitted indications on January 29 2001; however, this was postponed. This postponement was thought to be at Aventis' request in order to discuss the potential for a resistant pneumococcal infection labeling which would boost product sales. The revised date for the meeting was April 26 2001, at which the Anti-Infective Drugs Advisory Committee of the FDA recommended approval of telithromycin for the treatment of CAP in patients 18 years of age or older. The committee failed to recommend approval for the use of the drug for the remaining three indications for which it was filed, citing concerns over potential cardiovascular risk and liver toxicity; at this time, the company was in active discussions with the FDA regarding approval of the remaining three indications. An approvable letter for CAP, acute bacterial exacerbations of chronic bronchitis and acute bacterial sinusitis was received by the company in June 2001; Aventis also received a non-approvable letter for the treatment of tonsillitis/pharyngitis at this time. In April 1999, ABN Amro predicted annual sales of DM 50 million in 2001, rising to DM 100 million in 2002. In February 1999, Lehman Brothers estimated a 70% probability that this ketolide would come to market. The analysts also estimated a launch date of 2001, with peak sales of US $700 million in 2009. Analysts Merrill Lynch predicted in September 200, that the product would be launched by 2001, with sales of euro 50 million in that year, rising to euro 284 million in 2004. Deutsche Bank predicted in August 2001, that sales of the product would reach euro 5 million in 2001, rising to euro 300 million in 2005. Analysts at Merrill Lynch predicted in November 2001, that the product would be resubmitted in the US in mid-2002, and would make sales of US $5 million in 2001, rising to US $250 million in 2004.